When saliva meets acid: chemical warfare at the oesophagogastric junction

Abstract

In the Western world at least, most upper gastrointestinal cancers now arise from the mucosa near to the oesophagogastric junction. Research into the mechanism of the development of adenocarcinoma at the oesophagogastric junction has mainly focused on the noxious effects of acid and bile. There is however an alternative concept for explaining the location of adenocarcinomas: the cancers are occurring at the anatomical site where saliva encounters acidic gastric juice and their interaction generates reactive nitrogen species which are potentially mutagenic and carcinogenic. At present, it is unclear whether the active nitrite chemistry is exerting detrimental effects on the surrounding tissue but it is important to investigate this possibility as it could reveal new ways of preventing and treating the high prevalence of disease occurring at this anatomical site.

Figure 1

Of all the nitrate absorbed from the diet or produced endogenously, 25% is taken up by the salivary glands and secreted into the mouth. Bacteria on the dorsum of the tongue convert 10–90% of this nitrate in saliva to nitrite. When saliva is swallowed and meets acidic gastric juice it is converted to nitrosating species (that is, N₂O₃ and NOSCN) and by further reacting with ascorbic acid in gastric juice to nitric oxide (NO). In patients with reflux disease this chemistry occurs within the oesophagus where gastric refluxate mixes with saliva.